Journal: Nature

Article Title: Replication-stress-induced chromatin loops protect fork stability

doi: 10.1038/s41586-026-10695-1

Figure Lengend Snippet: a , DNA FISH validation of a HU-specific loop in Hap1 cells. Left, representative images of left (green) and right (red) anchor probes (DAPI, blue). Right, the interprobe distance distribution. n = 108 (UT) and n = 119 (HU) S phase nuclei; n = 102 (UT), n = 81 (HU) non-S-phase nuclei. Statistical analysis was performed using two-sided Mann–Whitney U -tests; P = 0.0001 (S phase) and P = 0.4295 (non-S phase). Data were pooled from two independent experiments and normalized to their respective UT conditions (set to 1) to enable direct comparison across experiments. Scale bars, 5 μm. b , Representative HU-specific, G9a-dependent chromatin loops on chromosomes 9 (top) and 2 (bottom). The bottom tracks show H3K9me3 Rep-ChIC peaks, IZs and annotated genes. c , The fractions of IZs and TZs located within HU-unique loop bodies, anchors or neither. d , The aggregate average CTCF Rep-ChIC signal within HU-unique loops and ±10 kb around their anchors. Statistical analysis was performed using the two-sided Mann–Whitney U -test; P = 1.96 × 10 −16 . The results shown are from one biological replicate. e , The distribution of IZs and CTCF motifs within HU-specific loops and flanking regions. Consensus CTCF motifs at loop anchors enriched in the CTCF Rep-ChIC signal and their orientations (convergent versus tandem) are shown below. Heat maps of the CTCF Rep-ChIC signal around loop anchors (±1 kb) in UT and HU-treated MRC5 cells are also shown. f , g , APA of HU-specific loops in HCT116 CTCF-mAID2-mClover cells ( f ) and MRC5 cells ( g ). The enrichment relative to the background is indicated in the top-right corners. Results shown are from one biological replicate. h , Schematic of a loop with CTCF sites (top). Bottom, heat maps of IZs, H3K9me3, FANCD2 Rep-ChIC and the strand-specific fork pausing signal (TrAEL-seq) within HU-unique loops and flanking regions (±3.5 kb). C, Crick strand; W, Watson strand. i , Fork pausing signal within and flanking HU-unique loops with (+CTCF) or without (−CTCF) CBSs at the loop anchor, and UT-HU common loops. Results shown are a representative dataset out of two independent biological replicate. j , The average TrAEL-seq Watson (blue) and Crick (orange) strand profiles across HU-unique loops ±5 kb. All experiments used MRC5 cells unless otherwise stated.

Article Snippet: In experiments using HCT116 cells expressing CTCF-mAID2-mClover, the culture medium was replaced with medium containing 1 μM 5-Ph-IAA (HY-134653, MedChemExpress) for at least 2 h before the experiment to induce transient depletion of CTCF.

Techniques: Biomarker Discovery, MANN-WHITNEY, Comparison

Journal: Nature

Article Title: Replication-stress-induced chromatin loops protect fork stability

doi: 10.1038/s41586-026-10695-1

Figure Lengend Snippet: a , Distribution of TADs by replication timing (early, late, TTR: Timing Transition Regions) ± HU for two replicates (MRC5 cells). b, c , Insulation score ( b ) and CTCF Rep-ChIC signal ( c ) ± 10 kb of HU-unique loops overlapping (blue/top) or not overlapping (green/bottom) TAD borders. Aggregate average (top) and tornado plots (bottom) are shown. A1 and A2 indicate the loop anchors. Data shown are from one biological replicate. d , Top: CTCF-EdU PLA signal (red) in nuclei (blue). Bottom: Distribution of total PLA spot intensity per nucleus. S-phase nuclei analysed n = 986, 1416, 1556, 1524, 1204 and 846 (left to right) from one representative experiment which has been performed 2 times with similar results. ****P ≤ 0.0001, ns=non-significant (Kruskal–Wallis, Dunn’s test, P values from left to right: <0.0001, <0.0001, <0.0001, 0.3113). Experiments in HCT116-CTCF-mAID2-mClover cells. e , Western blot of CTCF depletion via 5-Ph-IAA, in HCT116-CTCF-mAID2-mClover cells. For gel source data, see Supplementary Fig. [n = 3] independent replicates. f , Heatmaps of average CTCF/FANCD2 Rep-ChIC, Fork-Deg-seq (WT vs. shBRCA2, in RPE1-shBRCA2 cells), γH2AX , and tumour SNVs across HU-unique loops with (+CTCF) or without (-CTCF) CTCF Binding Sites (CBSs) at the anchors for 3 biological replicates. g, h , Heatmaps of IZs (TrAEL-seq MRC5 IZ (g) or HCT116 IZ (h)), H3K9me3, FANCD2 Rep-ChIC, and strand-specific fork pausing signal (W for Watson strand and C for Crick strand, MRC5 cells) within HU-unique loops ± 3.5 kb in MRC5 ( g ) and HCT116-CTCF-mAID2-mClover ( h ) cells. i , Average TrAEL-seq Watson (blue) and Crick (orange) profiles ± 5 kb of HU-unique loops in HCT116-CTCF-mAID2-mClover cells (see Fig. ). All experiments in MRC5 cells unless otherwise stated.

Article Snippet: In experiments using HCT116 cells expressing CTCF-mAID2-mClover, the culture medium was replaced with medium containing 1 μM 5-Ph-IAA (HY-134653, MedChemExpress) for at least 2 h before the experiment to induce transient depletion of CTCF.

Techniques: Insulation, Western Blot, Binding Assay

Journal: Nature

Article Title: Replication-stress-induced chromatin loops protect fork stability

doi: 10.1038/s41586-026-10695-1

Figure Lengend Snippet: a , Rolling mean of z-scored DAPI intensity vs. S-phase progression from scEdU-seq tracks. Ribbon indicates s.d. b , Number of forks per cell vs. S-phase progression. Line is median; ribbon is 95% CI. c , Heatmap of maximum normalized scEdU-seq log counts binned per 40 kb along a 60 Mb region of chromosome 2, ordered by S-phase progression. Colour scale: Normalized read coverage across the region. d, e , DNA replication speeds at indicated loop anchors and background regions. Number of regions analysed: d, [n = 345 and 192 for UT and 0.5mMHU respectively] and e, n = 302, 283, 302, 214, 203 and 215 (left to right). Results shown are from one representative experiment which has been performed 2 times with similar results. f, g , Schematic of DNA fibre degradation assay in HCT116-CTCF-mAID2-mClover (top). IdU/EdU track length ratio distributions. Means ± s.d. shown (bottom). Number of tracks analysed: Panel f: n = 1015, 1058, 1057, 1057, 1116, 1080, 1117, 1079, 1101, 1086, 1069 and 1061 (left to right), pooled from 3 independent biological replicates and overlaid in three different colours in the plot. Panel g: n = 681, 726, 708, 724, 641, 669, 643, 676, 682, 684, 683, 666, 703, 676, 676, 689, 673, 686, 713 and 665 (left to right) pooled from 2 independent biological replicates and overlaid in two different colours. ****P ≤ 0.0001, **P ≤ 0.01, ns=non-significant (Kruskal–Wallis, Dunn’s test, panel f: All P values < 0.0001, panel g: P values: (left to right) >0.9999, <0.0001, <0.0001, <0.0001, <0.0001, 0.0095, 0.0061, <0.0001, >0.9999, <0.0001, 0.4485, >0.9999, 0.0019, >0.9999, >0.9999, >0.9999). h , Schematic of Fork-Deg-seq approach to map nucleolytic degradation at newly replicated regions. The diagram was created using BioRender; Taneja, N. https://BioRender.com/d7kf3t0 (2026). i , Fork-Deg-seq signal in WT and shBRCA2-induced RPE1 cells after 8 h 4 mM HU, alongside BrdU IP signal and replication timing for the indicated region on chromosome 3. Dotted square highlights a loop-poor region with enhanced Fork-Deg-seq enrichment. Loops of bidirectional replicon (fountain)- scale are shown in dark red; smaller loops are shown in light red. j , Aggregate heatmap of CTCF (CTCF-Rep-ChIC, in MRC5 cells), ForkDeg-seq signal (in RPE1-shBRCA2 cells), γH2AX , and Single Nucleotide Variant (SNV ) distribution within and in a +/− 1 kb region flanking the HU-specific loops identified in MRC5 cells. Schematics: loop body and flanking regions. Orange triangles mark loop anchors position based on CTCF-binding sites. Colour scale: Normalized read coverage across the region. All experiments in MRC5 cells unless otherwise stated.

Article Snippet: In experiments using HCT116 cells expressing CTCF-mAID2-mClover, the culture medium was replaced with medium containing 1 μM 5-Ph-IAA (HY-134653, MedChemExpress) for at least 2 h before the experiment to induce transient depletion of CTCF.

Techniques: Degradation Assay, Variant Assay, Binding Assay

Journal: Nature

Article Title: Replication-stress-induced chromatin loops protect fork stability

doi: 10.1038/s41586-026-10695-1

Figure Lengend Snippet: a , Schematic of the replication fork degradation DNA fibre assay in HCT116 CTCF-mAID2-mClover cells, involving CTCF depletion (dep; 5-Ph-IAA) and G9a inhibition (UNC0642) (top). Middle, representative fibres. Bottom, the IdU/EdU track length ratio. Data are mean ± s.d. From left to right, numbers of forks analysed per condition: n = 1,014, 1,015, 1,034, 1,039, 1,032, 1,053, 1,070 and 1,005, pooled from three independent replicates and overlaid in three different colours in the plot. Statistical analysis was performed using Kruskal–Wallis tests followed by Dunn’s test; from left to right, P < 0.0001, P < 0.0001, P < 0.0001, P < 0.0001, P < 0.0001, P > 0.9999, P > 0.9999, P > 0.9999. Scale bar, 5 μm. b , Representative locus (chromosome 16: 81.3–82.75 Mb). Top, Hi-C heat map (the red squares highlight the positions of the loop anchors). The Fork-deg-seq signal in HCT116-CTCF-mAID2-mClover cells UT or treated with G9ai (4 h), 5-Ph-IAA (4 h, CTCF-depleted) or both after 4 mM HU (5 h or 8 h). MRC5 CTCF and H3K9me3 Rep-ChIC signals are shown below, alongside IZs and fragile sites. The black arrowheads indicate high Fork-deg-seq signal. The shaded area shows a loop-dense region with reduced degradation; unshaded areas show enhanced Fork-deg-seq enrichment. c , BrdU-enriched 5-kb bins classified by HU-unique loop coverage: loop-poor (0–1 loop, left, n = 4,398 bins) and loop-dense (≥2 loops, right, n = 6,844 bins). The fold change in Fork-deg-seq signal relative to the WT is shown. Data are mean ± s.d. Statistical analysis was performed using two-sided Mann–Whitney U -tests; loop-free region, from top to bottom: P = 4.4 × 10 −33 , P = 2.4 × 10 −132 , P = 2.4 × 10 −132 , P = 4.1 × 10 −33 , P = 2.4 × 10 −132 , P = 2.7 × 10 −34 ; loop-dense region, from left to right: P = 1.4 × 10 −130 , P = 2.0 × 10 −130 , P = 1.8 × 10 −130 , P = 3.2 × 10 −1 , P = 7.8 × 10 −2 , P = 8.4 × 10 −1 . Results shown are from one biological replicate. d , Aggregate analysis of the mean ± s.d. Fork-deg-seq signal within HU-unique loops and 5 kb flanking regions after 3 h of treatment with 4 mM HU alone (top row, left four plots) or with mirin and DNA2i followed by 4 mM HU (bottom row). Ionizing radiation (10 Gy) was included as a control without further treatment (top right plot). The results shown are from one biological replicate. All of the experiments described in this figure were performed in HCT116 CTCF-mAID2-mClover cells, unless otherwise stated.

Article Snippet: In experiments using HCT116 cells expressing CTCF-mAID2-mClover, the culture medium was replaced with medium containing 1 μM 5-Ph-IAA (HY-134653, MedChemExpress) for at least 2 h before the experiment to induce transient depletion of CTCF.

Techniques: Inhibition, Hi-C, MANN-WHITNEY, Control

Journal: Nature

Article Title: Replication-stress-induced chromatin loops protect fork stability

doi: 10.1038/s41586-026-10695-1

Figure Lengend Snippet: a , Representative locus (chr8: 122.8-133.9 Mb). Top: Hi-C heatmap (red squares highlight positions of loop anchors). Below: Fork-Deg-seq signal (HCT116-CTCF-mAID2-mClover cells) untreated or treated with G9ai (4 h), 5-Ph-IAA (4 h, CTCF-dep) or both upon 4 mM HU (5 h or 8 h), alongside MRC5 CTCF and H3K9me3 Rep-ChIC signals, IZs and fragile sites. Black arrowheads indicate high Fork-Deg-seq signal. Shaded area: loop-dense region with reduced degradation; unshaded areas show increased degradation. b , Aggregate mean Fork-Deg-seq signal ± s.d. after 5 h 4 mM HU within HU-unique loops ± 5 kb in HCT116-CTCF-mAID2-mClover cells. Results shown are from one representative experiment which has been performed 2 times with similar results. c-e , Distribution of IZs at early [n = 2119] and late [n = 2193] replicating fragile sites. ( c ) HU-unique loops overlapping IZs (MRC5), ****P ≤ 0.0001, (Two-sided Mann–Whitney U test, p-value: 7.858e-38). ( d ) Fork-Deg-seq signal in HCT116 IZs, ****P ≤ 0.0001, (Two-sided Mann–Whitney U test, p-values: 1.222e-07, 6.247e-06, 1.161e-05, 6.247e-06 left to right). ( e ) Fork-Deg-seq signal in RPE1 IZs (RPE1-shBRCA2 cells), ****P ≤ 0.0001, (Two-sided Mann–Whitney U test, p-values: 3.119e-37 WT + HU and 2.080e-55 shBRCA2+HU). f , Representative electron micrographs showing a reversed fork with ssDNA gaps on both daughter strands and intact reversed arms (HCT116-CTCF-mAID2-mClover). P, parental strand; D, daughter strand; R, reversed arms. Scale bars: 250 nm or 1183 bp (main), 50 nm or 473 bp (insets). g , Ranked gap length distribution per condition. h , qPCR analysis of HU-unique loop formation in WT and TKO (SMARCAL1, ZRANB3, HLTF knockout) U2OS cells ± 4 mM HU. Means ± s.e.m. [n = 4 independent biological replicates]. ****P < 0.0001, ***P < 0.001, **P < 0.01, ns=non-significant (Ordinary one-way ANOVA, Tukey’s test, P value from top to bottom: a: <0.0001, 0.0026, 0.4735; b: 0.0003, 0.0095, 0.5794; c: 0.004, 0.1237, 0.3688; d: <0.0001, 0.0471, 0.1211; e: <0.0001, 0.0003, 0.0752; f: 0.0004, 0.0003, 0.5844; g: <0.0001, 0.0042, 0.4301; h: 0.0003, 0.0004, 0.935; i: <0.0001, 0.0019, 0.4734,; j: 0.0006, 0.0001, 0.6204; k: 0.0005, 0.0206, 0.4417; l: <0.0001, 0.0032, 0.3017; m: <0.0001, 0.0173, 0.269; n: 0.0013, 0.0074, 0.8887; o: 0.0013, 0.0074, 0.7701; p: 0.0003, 0.095, 0.1693). i , Top: Schematic showing that only H3K9me3 signal intensity overlapping with EdU was measured. Bottom: Distribution of H3K9me3 intensity in the region of interest and for the indicated conditions. Number of replication sites analysed per condition across two independent experiments: n = 148, 98, 111, 107, 103 and 84 from left to right. (*: p < 0.05, ****: p < 0.0001, ns: non-significant. Kruskal–Wallis test followed by Dunn’s test, P values: 0.0160, <0.0001, <0.0001, >0.9999, 0.7905, >0.9999, 0.0946, >0.9999 and 0.0156 (top to bottom)). j , Top: Schematic showing that only the H3K9me3 signal intensity just outside of the EdU track was measure (H3K9me3 intensity over a region covering 20% of the total length of the EdU track was measured on both side of the EdU track). Bottom: Distribution of H3K9me3 intensity in the region of interest and for the indicated conditions. Number of replication sites analysed per condition across two independent experiments: n = 98, 119, 107 and 103 from left to right. (***: p < 0.001, ****: p < 0.0001, ns: non-significant. Kruskal–Wallis test followed by Dunn’s test, P values: <0.0001, 0.7726, 0.4606, 0.0003, <0.0001 and <0.0001 (top to bottom). k , Total intensity distribution of CTCF-EdU PLA spots. S-phase nuclei analysed: n = 642 for all conditions imaged from one representative experiment, which has been performed 2 times with similar results. Red line marks mean. ****P ≤ 0.0001, **P ≤ 0.01, ns=non-significant (Kruskal–Wallis, Dunn’s test, P values from left to right: <0.0001, <0.0001, 0.0011, <0.0001, <0.0001, 0.1690).

Article Snippet: In experiments using HCT116 cells expressing CTCF-mAID2-mClover, the culture medium was replaced with medium containing 1 μM 5-Ph-IAA (HY-134653, MedChemExpress) for at least 2 h before the experiment to induce transient depletion of CTCF.

Techniques: Hi-C, MANN-WHITNEY, Knock-Out

Journal: iScience

Article Title: ALDH3A2-mediated fatty acid synthesis induces ferroptosis and AML drug resistance

doi: 10.1016/j.isci.2026.116202

Figure Lengend Snippet: Expression of ALDH3A2 in healthy people and patients with AML (A) The expression of ALDH3A2 in various tumors compared with normal tissues. Data are represented as mean ± SEM. (B) Expression of ALDH3A2 in 88 leukemia cell lines. (C) The survival curve of patients with high and low expression of ALDH3A2 (n [low expression] = 121, n [high expression] = 30). (D) The expression of protein ALDH3A2 in HL-60, HL-60/ADM, K562, K562/ADM, and bone marrow in patients. (E) The expression of ALDH3A2 RNA in bone marrow mononuclear cells of AML patients in the CR ( n = 9), C1NR ( n = 8), and R/R ( n = 10) group. Data are represented as mean ± SEM. (F) The expression of ALDH3A2 in bone marrow mononuclear cells of 3 AML patients at their initial and recurrent stage. (G) High/low expression of ALDH3A2 and molecular mutation distribution of 66 AML patients. Data are represented as mean ± SEM. Ns indicates no statistical difference between the two groups, ∗ indicates p < 0.05 between the two groups. Statistical significance was determined using unpaired two-tailed Student’s t tests for the comparison of two groups.

Article Snippet: ALDH3A2 expression in human leukemia cell lines and peripheral blood mononuclear cells , Human Protein Atlas website ( https://www.proteinatlas.org/ ) , .

Techniques: Expressing, Mutagenesis, Two Tailed Test, Comparison

Journal: iScience

Article Title: ALDH3A2-mediated fatty acid synthesis induces ferroptosis and AML drug resistance

doi: 10.1016/j.isci.2026.116202

Figure Lengend Snippet: ALDH3A2-V protects AML cells from ferroptosis and cytotoxicity induced by doxorubicin (A) ALDH3A2 mRNA relative expression in HL-60/ADM and K562/ADM cells after transfection of siRNA by electroporation. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . (B) The lipid peroxidation degree of HL60ADM and K562ADM cells in the control (ctrl) and ALDH3A2 knockdown (KD) groups after the same dose of doxorubicin treatment for 48 h. (C) The content of ALDH3A2 protein in HL-60, K562, U937, and KG-1α in the ALDH3A2 overexpressing (OE) group and the control (CON) group. (D) The location of ALDH3A2-V overexpression. This representative image was selected from 3 independent replicate experiments, with 4 fields of view evaluated per replicate. (E) Lipid peroxidation in HL-60, K562, U937, and KG-1α in the ALDH3A2 OE group and the CON group under the same concentration of doxorubicin treatment. (F and G) Cell viability and its fitting curve of HL-60, K562, U937, and KG-1α in the ALDH3A2 OE group and the CON group under the gradient concentration of doxorubicin treatment. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . Ns indicates no statistical difference between the two groups, ∗ indicates p < 0.05 between the two groups, and ∗∗ indicates p < 0.01 between the two groups. Statistical significance was determined using unpaired two-tailed Student’s t tests for the comparison of two groups.

Article Snippet: ALDH3A2 expression in human leukemia cell lines and peripheral blood mononuclear cells , Human Protein Atlas website ( https://www.proteinatlas.org/ ) , .

Techniques: Expressing, Transfection, Electroporation, Control, Knockdown, Over Expression, Concentration Assay, Two Tailed Test, Comparison

Journal: iScience

Article Title: ALDH3A2-mediated fatty acid synthesis induces ferroptosis and AML drug resistance

doi: 10.1016/j.isci.2026.116202

Figure Lengend Snippet: ALDH3A2 affects the sensitivity of AML cells to doxorubicin by altering 4-HNE and fatty acid content (A) The content of 4-HNE in cell lysate and culture supernatant of AML cells in the doxorubicin treatment (ADR) group and control (CON) group. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . (B) The content of 4-HNE in HL-60, U937, and KG-1α of the overexpressing ALDH3A2 (OE) group and the CON group under the same concentration of doxorubicin treatment. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . (C) OPLS-DA was performed on the measured fatty acids. Quantitative data for fatty acid and cell viability were collected from 3 independent experiments. (D) Variable Importance in Projection（VIP) value of different fatty acids; the difference is considered significant when the VIP>1. (E) Content of three different fatty acids in the CON and OE ALDH3A2 group. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . (F) Cell viability of AML cells in heptadecanoic acid, oleic acid, and linoleic acid-pretreated groups and the CON group after the treatment of doxorubicin. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . (G) Lipid peroxidation in AML cells in heptadecanoic acid-, oleic acid-, and linoleic acid-pretreated groups and the CON group after the treatment of doxorubicin. These images were selected from 3 independent replicates. Ns indicates no statistical difference between the two groups, ∗ indicates p < 0.05 between the two groups, ∗∗ indicates p < 0.01 between the two groups, and ∗∗∗ indicates p < 0.001 between the two groups. Statistical significance was determined using unpaired two-tailed Student’s t tests for the comparison of two groups.

Article Snippet: ALDH3A2 expression in human leukemia cell lines and peripheral blood mononuclear cells , Human Protein Atlas website ( https://www.proteinatlas.org/ ) , .

Techniques: Control, Concentration Assay, Two Tailed Test, Comparison

Journal: iScience

Article Title: ALDH3A2-mediated fatty acid synthesis induces ferroptosis and AML drug resistance

doi: 10.1016/j.isci.2026.116202

Figure Lengend Snippet: Effects of fatty acids and ALDH3A2 on plasma membrane fluidity and drug uptake (A) Laurdan staining showed different ratios of order and disorder phases in the control, heptadecanoic acid-, oleic acid-, or linoleic acid-treated groups. These representative images were selected from 3 independent replicate experiments, with 4 fields of view evaluated per replicate. (B) Flow cytometry was employed to quantify Cy5 fluorescence intensity in control, heptadecanoic acid-, oleic acid-, or linoleic acid-pretreated groups at 2- and 4-h intervals following doxorubicin exposure. The representative image was selected from 3 independent replicate experiments. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . (C) Laurdan staining showed different ratios of order and disorder phases in the control and ALDH3A2 high groups. The mCherry fluorescent protein was co-expressed with ALDH3A2, which indicates successful transfection of the overexpression plasmid into the cells. These representative images were selected from 3 independent replicate experiments, with 4 fields of view evaluated per replicate. (D) U937 cells in the control group and ALDH3A2 high group were treated with Cy5-labeled doxorubicin. The mCherry fluorescent protein was co-expressed with ALDH3A2, which indicates successful transfection of the overexpression plasmid into the cells. These representative images were selected from 3 independent replicate experiments, with 4 fields of view evaluated per replicate. Ns indicates no statistical difference between the two groups, ∗ indicates p < 0.05 between the two groups, and ∗∗ indicates p < 0.01 between the two groups. Statistical significance was determined using unpaired two-tailed Student’s t tests for the comparison of two groups.

Article Snippet: ALDH3A2 expression in human leukemia cell lines and peripheral blood mononuclear cells , Human Protein Atlas website ( https://www.proteinatlas.org/ ) , .

Techniques: Clinical Proteomics, Membrane, Staining, Control, Flow Cytometry, Fluorescence, Transfection, Over Expression, Plasmid Preparation, Labeling, Two Tailed Test, Comparison

Journal: iScience

Article Title: ALDH3A2-mediated fatty acid synthesis induces ferroptosis and AML drug resistance

doi: 10.1016/j.isci.2026.116202

Figure Lengend Snippet: In in vivo experiments, AML with high expression of ALDH3A2 exhibits a poorer response to doxorubicin (A) Schematic diagram of the process for establishing the AML mouse model. (B) In vivo bioimaging shows the success of the model and the leukemia burden in mice before and after treatment. (C) Statistics of fluorescence values ( n = 5) on days 3 and 7 of the experiment. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . (D) Survival curves of mice in different groups. (E) 4-HNE content in plasma of mice in different groups ( n = 5) on day 7. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . (F) 4-HNE content in plasma of AML patients with low ( n = 5) and high ( n = 5) ALDH3A2 expression levels before and after receiving chemotherapy. Ns indicates no statistical difference between the two groups, ∗ indicates p < 0.05 between the two groups, and ∗∗ indicates p < 0.01 between the two groups. Statistical significance was determined using unpaired or paired two-tailed Student’s t tests for the comparison of two groups.

Article Snippet: ALDH3A2 expression in human leukemia cell lines and peripheral blood mononuclear cells , Human Protein Atlas website ( https://www.proteinatlas.org/ ) , .

Techniques: In Vivo, Expressing, Fluorescence, Clinical Proteomics, Two Tailed Test, Comparison

Journal: iScience

Article Title: ALDH3A2-mediated fatty acid synthesis induces ferroptosis and AML drug resistance

doi: 10.1016/j.isci.2026.116202

Figure Lengend Snippet: X24003 inhibits ALDH3A2 and enhances the cytotoxic effects of doxorubicin on resistant AML cells (A) OPLS-DA was performed on the measured fatty acid containment in the X24003 treatment group and control group. Quantitative data for fatty acid and cell viability were collected from 3 independent experiments. VIP value of different fatty acids; the difference is considered significant when the VIP>1. (B) X24003 exhibits a synergistic effect with doxorubicin in the elimination of doxorubicin-resistant AML cell lines HL-60ADM and K562ADM. (C) X24003 augments doxorubicin-induced lipid peroxidation in doxorubicin-resistant AML cell strains without affecting the parental cell lines. The representative image was selected from three independent replicate experiments. (D) In vivo bioimaging shows the success of the model and the leukemia burden in mice before and after treatment.

Article Snippet: ALDH3A2 expression in human leukemia cell lines and peripheral blood mononuclear cells , Human Protein Atlas website ( https://www.proteinatlas.org/ ) , .

Techniques: Control, In Vivo

Journal: iScience

Article Title: ALDH3A2-mediated fatty acid synthesis induces ferroptosis and AML drug resistance

doi: 10.1016/j.isci.2026.116202

Figure Lengend Snippet: HDAC2 binds to the promoter of the ALDH3A2 gene and regulates its expression (A) CUT&RUN indicates that HDAC2 binds to the promoter of the ALDH3A2 gene; the binding affinity is observed to decrease after treatment with chidamide. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . (B) The expression of ALDH3A2 protein in AML cells following treatment with doxorubicin or chidamide. (C) Treatment of chidamide enhances lipid peroxidation induced by doxorubicin in AML cells. The representative image was selected from three independent replicate experiments. (D) Chidamide exhibits a synergistic effect with doxorubicin in the elimination of AML cells. Data are represented as mean ± SEM. The specific data are shown in the supplemental table . Ns indicates no statistical difference between the two groups, ∗ indicates p < 0.05 between the two groups, and ∗∗ indicates p < 0.01 between the two groups. Statistical significance was determined using unpaired two-tailed Student’s t tests for the comparison of two groups.

Article Snippet: ALDH3A2 expression in human leukemia cell lines and peripheral blood mononuclear cells , Human Protein Atlas website ( https://www.proteinatlas.org/ ) , .

Techniques: Expressing, Binding Assay, Two Tailed Test, Comparison